INSULIN-INDUCED DISSOCIATION OF SOS FROM GRB2 DOES NOT CONTRIBUTE TO THE DOWN-REGULATION OF RAS ACTIVATION

Activation of Ras by a number of receptor tyrosine kinases is mediated by the guanine nucleotide exchange factor Sos. This activation is tho ught to occur as a result of the recruitment to the plasma membrane of a complex consisting of Sos and the adaptor molecule Grb2. Growth fac tor stimulation has been shown to induce the rapid phosphorylation of Sos on serine and threonine residues. In rat L6 cells, insulin-induced Sos phosphorylation is accompanied by a partial dissociation of the G rb2-Sos complex. In this study we have investigated the relationship b etween Sos phosphorylation and Grb2 association. To this end, we have utilized cAMP because it has been demonstrated that elevation of cytop lasmic levels of cAMP inhibits growth factor-induced Sos phosphorylati on. We show that in rat L6 cells, cAMP treatment prevents both the ins ulin-stimulated Sos phosphorylation and Grb2 dissociation. However, cA MP treatment has no effect on the duration of insulin-induced Ras acti vation. These results suggest that the kinetics of Ras activation are independent of the phosphorylation-induced dissociation of Sos from Gr b2.